Biology subjects

Moulin, M.

Publications and source records attributed to Moulin, M..

7 recordsLinked to original sources

bioRxiv2026

Dynamic Compression Platform for Live Imaging of Scaffold-Transmitted Cellular Mechanoresponses

Mechanical characterization of biomaterial scaffolds is essential to evaluate their capacity to meet the functional demands of target tissues in tissue engineering and regenerative medicine applications. Scaffolds designed to interface with living tissues must support the transmission of mechanical cues to resident cells and stimulate mechanosignaling pathways that are essential to their function. In joints, bone and cartilage cells act as primary mechanosensors, converting mechanical stimuli into biochemical signals that regulate tissue homeostasis and remodelling. Therefore, evaluating cellular mechanoresponses to scaffold-transmitted compression in vitro can inform the development of functional tissue-engineered constructs. For example, poly({epsilon}-caprolactone) (PCL) scaffolds are highly relevant for bone and cartilage tissue engineering due to their biocompatibility, stable mechanical properties and slow degradation. Here, we applied a custom-built device to study compression-induced mechanosignaling in MC3T3-E1 pre-osteoblast cells. The device is composed of a polydimethylsiloxane (PDMS) pillar, a force-sensing load cell, and a piezoelectric linear track. A protocol is described in which MC3T3-E1 cells are repeatedly compressed, while in parallel live tracking of force measurements and live imaging of intracellular calcium dynamics in MC3T3-E1 cells are recorded. PCL scaffolds fabricated by melt electrowriting (MEW) were subsequently integrated into the platform. Scaffold-transmitted compression triggered dynamic increases in cytosolic calcium; in MC3T3-E1 cells located directly under the PCL microfibers, but also in cells located in the interfiber spaces. This device and workflow facilitate in vitro investigations of real-time cellular mechanoresponses to dynamic compression applied with biomaterial scaffolds, and provides a testing platform for evaluating the mechanotransductive properties of scaffolds intended for tissue engineering applications.

bioengineering↗

bioRxiv2026

Programmable bioprinting of tumor microenvironment arrays reveals laminin-dependent drug sensitivity

We present an active mixing toolhead for extrusion bioprinting. The tool enables the programmable fabrication of tumor microenvironment gradient arrays, through controlled deposition of mixed hydrogel precursor formulations into 384-well plates, pre-seeded with tumor cells. It operates on an open-source bioprinter and can actively mix arbitrary ratios of two hydrogel precursors prior to extrusion. These concentration gradient arrays are compatible with quantitative image analysis of cell viability and morphological responses to hydrogels conditioned with drug or extracellular matrix (ECM) proteins. The tools capacity to mix and print hydrogel precursor gradients was demonstrated using alginate and highly concentrated mCherry-conjugated mini-spidroin solutions. Hydrogel precursor stocks contained fluorescent reporters to facilitate quantifications of mixing efficiency, and as proxies for drug and ECM protein concentrations. The tool was applied to generate hydrogel-based gradients of the apoptosis-inducer staurosporine, from which concentration-dependent MDA-MB-231 breast cancer cell death responses were quantified. Gradient arrays of the ECM protein laminin-511, implicated in breast cancer tumorigenesis, were generated and revealed that increasing laminin-511 concentrations potentiated staurosporine-induced cell death. The study demonstrates the utility of this active mixing toolhead for producing hydrogel gradient arrays, and demonstrates the relevance of studying drug-responses in tumor microenvironment models that account for disease-specific ECM components.

bioengineering↗

bioRxiv2026

Broadband gamma-band EEG changes during magnetophosphene perception induced by 20 Hz magnetic field stimulation

ObjectiveMagnetophosphenes are visual percepts induced by extremely low-frequency magnetic fields (ELF-MF; <300 Hz), yet the EEG expression of suprathreshold magnetophosphene-inducing stimulation remains poorly characterized and is not reliably captured by classical low-frequency markers. We tested whether suprathreshold 20 Hz tAMS is accompanied by broadband high-frequency EEG changes rather than focal oscillatory effects. ApproachEEG was recorded in N=13 healthy volunteers during 20 Hz sinusoidal magnetic-field exposure delivered using transcranial alternating magnetic stimulation (tAMS) in a global-head configuration. Three conditions were analyzed: no exposure (0 mT), subthreshold (5 mT), and suprathreshold (50 mT). Gamma-band activity (30-80 Hz) was quantified using complementary spectral approaches, including aperiodic-adjusted gamma power. Main resultsPerception reports sharply dissociated the three conditions, with frequent perception at 50 mT only. Suprathreshold stimulation was associated with spatially distributed increases in gamma-band activity over frontal and occipito-parietal electrodes. These effects persisted after aperiodic correction using two independent parameterization methods and did not exhibit a consistent narrowband peak, indicating broadband high-frequency changes. No focal power change over primary occipital electrodes remained significant after Bonferroni correction. SignificanceSuprathreshold magnetophosphene-inducing stimulation is not reliably captured by focal low-frequency EEG markers but is accompanied by distributed broadband high-frequency activity. Because stimulation intensity and perceptual reports were strongly coupled, these effects should be interpreted as EEG correlates of a suprathreshold stimulation-perception state rather than as isolated markers of perception.

neuroscience↗

bioRxiv2025

EMILIN1 emerges as a TGFbeta/SETDB1-regulated secreted biomarker in Duchenne Muscular Dystrophy

Duchenne Muscular Dystrophy (DMD) is an incurable muscle-wasting disorder characterized by chronic membrane damage, inflammation, and progressive fibrosis. Fibrosis in DMD is driven by sustained TGF{beta} signaling, which promotes extracellular matrix (ECM) accumulation. We previously showed that SETDB1 sustains the TGF{beta}-induced fibrotic response in DMD myotubes. Here, we further show that SETDB1 modulates the TGF{beta}-induced secretome, particularly by regulating ECM-related proteins. Comparison of the basal secretome from DMD patient-derived myotubes and healthy controls revealed a distinct disease-specific profile. Integrating both secretome analyses, we identified EMILIN1, an ECM glycoprotein not previously studied in skeletal muscle, as a robust shared candidate; EMILIN1 is enriched in the DMD secretome, further upregulated by TGF{beta}, and downregulated upon SETDB1 depletion. We confirmed EMILIN1 overexpression in DMD patient muscle biopsies, validating its pathological relevance. Functionally, EMILIN1 depletion modulated myogenic differentiation and reduced expression of the fibrotic marker SERPINE1. These findings establish EMILIN1 as a novel secreted regulator of myogenesis and fibrosis, and implicate SETDB1 in shaping the TGF{beta}-dependent secretome in DMD. Our integrative proteomic approach provides new insights into the molecular drivers of impaired regeneration in DMD and highlights potential therapeutic targets.

genetics↗

bioRxiv2025

Modulation of error sensitivity during motor learning across time, space and environment variability

We never experience the exact same situation twice. In our dynamic and constantly changing environment, we continuously need to adapt our behavior, either due to external (e.g., a change of wind) or internal factors (e.g., muscle noise). Motor adaptation is the process of recalibration of movements in response to such perturbation. It activates when an agent needs to change their movement in response to a perceived error. It has been proposed that in order to perform motor adaptation, the brain continuously updates an error sensitivity signal that controls how much is learned from a past error. Such error sensitivity reflects the speed of learning, and understanding its dynamics is crucial to promoting efficient learning. In our experiment, healthy participants performed a visuomotor adaptation task requiring reaching multiple targets using a joystick. They experienced two periods of stable perturbations and two periods of random perturbations. In agreement with past research, we found that error sensitivity is lower in unstable environments. Moreover, error sensitivity is higher in a stable environment without perturbation than in a stable environment with perturbations. We observed a continuous increase of the error sensitivity within a stable perturbation environment. Finally, continuous spatial (across target locations) and temporal (across trials with same target) generalization of learning is present not only in stable but also in the random environment.

neuroscience↗

bioRxiv2024

Hierarchical structural organization in bioinspired peptide coacervate microdroplets

This study explores the dynamic and hierarchical structural organization of peptide coacervate microdroplets at the meso-to atomic-scale resolution using a combination of Transferred Nuclear Overhauser Effect Spectroscopy (TrNOESY), Small Angle Neutron Scattering (SANS), and confocal microscopy. Dynamic interactions driving the self-association of peptide clusters are revealed, highlighting the critical roles of interacting residues. These phase-separating model peptides form small oligomers at low pH, which aggregate into larger clusters at neutral pH. These clusters organize into a porous network within the droplets, facilitating size-selective cargo sequestration. The findings underscore the significance of the dynamic spatio-temporal properties of peptide-based coacervates, contributing to our understanding of phase separation at the atomic and molecular levels. Critically, this approach enables the investigation of coacervate structures in their native state, offering insights into the physical and dynamic interactions governing droplet formation and cargo encapsulation. TOC O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=106 SRC="FIGDIR/small/602323v4_ufig1.gif" ALT="Figure 1"> View larger version (43K): org.highwire.dtl.DTLVardef@15aadb2org.highwire.dtl.DTLVardef@41be55org.highwire.dtl.DTLVardef@36f0d8org.highwire.dtl.DTLVardef@fe1af8_HPS_FORMAT_FIGEXP M_FIG C_FIG

biochemistry↗

bioRxiv2023

Liver sinusoidal endothelial cells constitute a major route for hemoglobin clearance

Mild rupture of aged erythrocytes occurs physiologically in the spleen, leading to the release of hemoglobin (Hb), while pathological hemolysis characterizes several diseases. The detoxification of Hb has traditionally been attributed to the sequestration of Hb-haptoglobin complexes by macrophages. However, this process remains incompletely studied in animal models or primary cells, leaving the precise mechanisms of Hb clearance elusive. Using mice and primary liver cell cultures (murine and human), we uncovered that Hb uptake is chiefly performed by liver sinusoidal endothelial cells (LSECs) and involves macropinocytosis. Consistently, mouse LSECs displayed proteomic signatures indicative of active heme catabolism, ferritin iron storage, antioxidant defense, and macropinocytic capacity. LSECs also exhibited high iron content and the expression of hepcidin-regulated iron exporter ferroportin. Using erythrocyte/Hb transfusion assays in mice, we demonstrated that while splenic macrophages excel in phagocytosis of erythrocytes, LSECs primarily scavenge Hb and Kupffer cells clear erythrocyte membranes, the spleen-borne hemolysis products delivered to the liver via the portal circulation. High-dose Hb injections resulted in transient hepatic iron retention, early LSEC-specific induction of heme-catabolizing Hmox1 and iron-sensing Bmp6, culminating in hepcidin-mediated temporary hypoferremia. Transcriptional induction of Bmp6 in mice was phenocopied by erythrocyte lysis upon phenylhydrazine or iron citrate injection, although the latter elicited a distinct LSEC transcriptional signature compared to Hb. In conclusion, we identify LSECs as key Hb scavengers, a function that establishes the spleen-to-liver axis for iron recycling and contributes to heme detoxification during hemolysis, coupled with the induction of the BMP6-hepcidin axis to restore iron homeostasis.

cell biology↗